Chemotherapy dose intensity and quality cancer care.
Myelosuppression continues to represent the major dose-limiting toxicity of cancer chemotherapy. Neutropenia and its complications, including febrile neutropenia, occur most often early in the course of treatment but are often underreported in clinical trials. In addition to associated morbidity, mortality, and cost, myelosuppression is often associated with reduced chemotherapy dose intensity. Reduction in chemotherapy dose intensity may compromise disease control and survival in patients with curable malignancies. Several investigators have argued, based on retrospective reviews of large clinical trials, that myelosuppression and neutropenia are surrogates for delivered dose intensity with patients encountering neutropenic events uniformly experiencing better survival. While the number of randomized trials in which patients were deliberately assigned to reduced dose intensity are limited, they consistently demonstrate poorer long-term outcomes in patients with responsive and potentially curable malignancies. The design and implementation of such studies are limited by both ethical concerns and study power and sample size considerations. Recent interest in dose dense schedules also suggests that such an approach may further increase the proportion of patients surviving for 5 years or more. Despite the compelling data available, national practice pattern surveys in the United States have consistently demonstrated a high frequency of dose reductions and delays such that more than half of patients being treated with curative intent receive significantly reduced dose intensity. This review will summarize and discuss the reasons for such undertreatment and strategies available to avoid dose reductions and delays. Randomized controlled trials as well as meta-analyses of those trials have demonstrated that the myeloid growth factors, in addition to reducing the risk and consequences of febrile neutropenia, are capable of sustaining or increasing chemotherapy dose intensity. Recent economic studies suggest that due to the impact of greater relative dose intensity on long-term outcomes, growth factor support to sustain dose intensity is both an effective and cost-effective management strategy. The delivery of optimal chemotherapy dose intensity in patients with potentially curable malignancies should be considered a major quality indicator in cancer patient care.
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